Integrated Transcriptomic and Metabolomic Profiling of the Placenta in a Dexamethasone-Induced Cleft Palate Rabbit Model

IF 1.6 4区医学 Q4 DEVELOPMENTAL BIOLOGY

Birth Defects Research Pub Date : 2025-03-29 DOI:10.1002/bdr2.2467

Lanling Lin, Mianxing Wei, Xiao Luo, Chong Zhang, Bingshuai Jing, Jue Wang, Bing Shi, Meng Gong, Chenghao Li

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引用次数: 0

Abstract

Background

Cleft palate is a congenital malformation influenced by both genetic and environmental factors. Although environmental contributors have been extensively studied, the placenta—an essential organ that mediates maternal–fetal interactions and offers protection against environmental insults—remains poorly understood in this context. This study aimed to explore transcriptomic and metabolomic alterations in the placenta following maternal exposure to corticosteroids, using a dexamethasone-induced cleft palate rabbit model.

Methods

Untargeted metabolomics and transcriptomics analyses were conducted on placental and amniotic fluid samples from fetuses with and without dexamethasone-induced cleft palate. Histopathological examination was performed to assess structural abnormalities in the placenta.

Results

The cleft palate group exhibited marked placental pathologies, including fibrosis, calcification, and necrosis. Transcriptomic analysis identified 4744 differentially expressed genes, enriched in pathways related to hormone signaling, vascular development, and inflammation. Metabolomic profiling revealed significant changes in both placenta and amniotic fluid, especially in the urea cycle, aspartate metabolism, and nicotinate and nicotinamide metabolism. The urea cycle was particularly disrupted in the cleft palate group.

Conclusion

These findings reveal a strong association between placental structural and functional abnormalities and cleft palate formation in the dexamethasone-induced model, offering novel insights into the potential role of the placenta in cleft palate pathogenesis.

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地塞米松诱导的兔唇模型胎盘的转录组学和代谢组学分析

背景腭裂是一种受遗传和环境因素共同影响的先天性畸形。虽然环境因素已被广泛研究，但胎盘-一个调节母胎相互作用并提供保护免受环境伤害的重要器官-在这方面仍然知之甚少。本研究旨在利用地塞米松诱导的兔唇模型，探讨母体暴露于皮质类固醇后胎盘的转录组学和代谢组学变化。方法对地塞米松诱发腭裂胎儿的胎盘和羊水进行非靶向代谢组学和转录组学分析。组织病理学检查评估胎盘结构异常。结果腭裂组胎盘病变明显，包括纤维化、钙化、坏死。转录组学分析确定了4744个差异表达基因，这些基因在激素信号、血管发育和炎症相关的通路中富集。代谢组学分析显示胎盘和羊水发生了显著变化，尤其是尿素循环、天冬氨酸代谢、烟酸和烟酰胺代谢。在腭裂组尿素循环被特别破坏。结论在地塞米松诱导的腭裂模型中，胎盘结构和功能异常与腭裂的形成有密切的联系，为胎盘在腭裂发病中的潜在作用提供了新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Birth Defects Research Medicine-Embryology

CiteScore

3.60

自引率

9.50%

发文量

153

期刊介绍： The journal Birth Defects Research publishes original research and reviews in areas related to the etiology of adverse developmental and reproductive outcome. In particular the journal is devoted to the publication of original scientific research that contributes to the understanding of the biology of embryonic development and the prenatal causative factors and mechanisms leading to adverse pregnancy outcomes, namely structural and functional birth defects, pregnancy loss, postnatal functional defects in the human population, and to the identification of prenatal factors and biological mechanisms that reduce these risks. Adverse reproductive and developmental outcomes may have genetic, environmental, nutritional or epigenetic causes. Accordingly, the journal Birth Defects Research takes an integrated, multidisciplinary approach in its organization and publication strategy. The journal Birth Defects Research contains separate sections for clinical and molecular teratology, developmental and reproductive toxicology, and reviews in developmental biology to acknowledge and accommodate the integrative nature of research in this field. Each section has a dedicated editor who is a leader in his/her field and who has full editorial authority in his/her area.